UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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Item 7.01. | Regulation FD Disclosure. |
As previously announced, Insmed Incorporated (the “Company”) presented a live webcast today, in conjunction with its 2020 R&D Day. In connection therewith, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.1 and incorporated herein by reference. In addition, the R&D Day webcast included a slide presentation, a copy of which is attached hereto as Exhibit 99.2 and incorporated herein by reference.
The information contained herein, including the exhibits attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.
Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
Exhibit No. |
Description | |
99.1 | Press release issued by Insmed Incorporated on September 30, 2020. | |
99.2 | Insmed Incorporated September 30, 2020 R&D Day Presentation. | |
104 | Cover Page Interactive Date File (embedded within the Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
INSMED INCORPORATED | |||
Dated: September 30, 2020 | By: | /s/ Christine Pellizzari | |
Name: | Christine Pellizzari | ||
Title: | Chief Legal Officer |
Exhibit 99.1
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Insmed Highlights Progress Across Portfolio and Outlines Growth Strategy at R&D Day
– Initiated Phase 1 study of treprostinil palmitil inhalation powder (TPIP); Phase 2a study in pulmonary arterial hypertension planned for 2021 –
– Expects to initiate registrational Phase 3 ASPEN trial of brensocatib in patients with non-cystic fibrosis bronchiectasis (NCFBE) in fourth quarter of 2020; expansion into additional neutrophil-mediated diseases planned in 2021 –
– Expanding commercial opportunity for ARIKAYCE with planned European launch by end of 2020 and potential Japanese launch in 2021, if approved, in refractory MAC lung disease; expects to initiate registrational program in front-line NTM in 2020 –
– Cash runway of over three years based on currently planned development programs –
BRIDGEWATER, N.J., September 30, 2020 /PRNewswire/ — Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, today announced progress across its portfolio of therapies and pipeline candidates, which will be discussed in further detail today at the Company’s virtual Research & Development (R&D) Day. The event will feature presentations from the Insmed management team and Ronald J. Oudiz, M.D., FACP, FACC, FCCP, Professor of Medicine at the David Geffen School of Medicine at the University of California Los Angeles (UCLA), the Interim Chief, Division of Cardiology, and a Director at the Liu Center for Pulmonary Hypertension at the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, and the lead investigator in the Company’s planned Phase 2a trial for treprostinil palmitil inhalation powder (TPIP).
“Our success in building a commercial company with a global footprint and strong pipeline sets the stage for Insmed’s next chapter of growth,” said Will Lewis, Chair and Chief Executive Officer of Insmed. “With ARIKAYCE, our global expansion efforts and upcoming study in front-line NTM patients has the potential to establish this first-in-disease program as the standard of care in NTM lung disease worldwide. We believe brensocatib, our DPP1 inhibitor, offers an entirely new approach to address a wide array of neutrophil-mediated diseases. We plan to build upon our early leadership position in this space with our anticipated near-term registrational study in NCFBE, followed by a new development program in cystic fibrosis and plans to explore other opportunities across the neutrophil-mediated disease landscape. We are also pleased to announce the initiation of a Phase 1 trial of TPIP, which represents an exciting opportunity to more fully harness the potential of the prostanoid pathway for the treatment of pulmonary arterial hypertension and may offer a disease-modifying effect. We are well capitalized to execute against our strategic objectives during this next phase of growth for Insmed.”
Select R&D Day Highlights
Initiated Phase 1 Trial for Treprostinil Palmitil Inhalation Powder
The Company announced today that it has initiated dosing of the first subjects in the Phase 1 healthy volunteer trial of TPIP in the United States. The objective of this first-in-human single ascending dose and multiple ascending dose study is to assess the pharmacokinetics and tolerability profile of TPIP. Top-line data are expected in the first quarter of 2021. The Company also announced plans to initiate a Phase 2a study in patients with pulmonary arterial hypertension (PAH) in early 2021.
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Today, Dr. Oudiz will provide a review of the PAH treatment landscape and the remaining unmet medical need. Additionally, the Company will provide an update on TPIP and review key highlights of preclinical data supporting the product candidate’s potentially differentiated product profile that could prove to be an advantageous addition to the therapeutic arsenal for the treatment of patients with PAH.
Treprostinil palmitil is a prodrug consisting of treprostinil linked by an ester bond to a 16-carbon chain. The prodrug becomes active when esterases cleave off the 16-carbon chain, resulting in the active molecule treprostinil. TPIP is formulated as a dry powder for administration in a capsule-based inhalation device.
Building a Leading Neutrophil-Mediated Portfolio with Brensocatib
Insmed will outline its plans to leverage the potential of brensocatib, its small molecule, oral, reversible inhibitor of dipeptidyl peptidase I (DPP1), in an array of neutrophil-mediated diseases, beginning with NCFBE. The Company will discuss the study design for its registrational Phase 3 trial of brensocatib for the treatment of NCFBE. The trial, known as ASPEN, was developed with input from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Insmed remains on track to launch the ASPEN trial in the fourth quarter of 2020.
The Company also announced plans to advance a clinical development program for brensocatib in cystic fibrosis (CF) and to discuss this program with health authorities in the first half of 2021.
Global Expansion for ARIKAYCE® (Amikacin Liposome Inhalation Suspension)
ARIKAYCE is the first and only FDA-approved therapy for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. Today the Company will provide an update on its global expansion efforts in Europe and Japan. Insmed recently received a positive opinion from the Committee for Medicinal Products for Human Use of the EMA for the treatment of nontuberculous mycobacterial (NTM) lung infections caused by MAC in adults with limited treatment options who do not have CF. The Company anticipates receiving Marketing Authorization in the European Union by the end of October, with a planned first European launch by end of 2020. In addition, Insmed filed a Japanese New Drug Application (JNDA) with the Japanese Ministry of Health, Labour and Welfare in March of this year. Following an anticipated 12-month review, if ARIKAYCE is approved, the Company would anticipate launching ARIKAYCE in Japan in the middle of 2021.
Additionally, the Company will provide details around its planned registration program to pursue regulatory approval of ARIKAYCE as a front-line therapy designed to establish a new standard of care for patients suffering from NTM lung disease. The clinical study design includes two separate but inter-related clinical trials to be conducted in parallel. ENCORE is the pivotal study intended to fulfill the post-marketing requirement to allow full approval of ARIKAYCE in the United States. The ARISE trial is an interventional study designed to validate the patient-reported outcome (PRO) tool that will be used to measure efficacy in ENCORE. The Company plans to initiate both trials globally in the fourth quarter of 2020.
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Financial Update
As of June 30, 2020, Insmed had cash and cash equivalents of $641.9M. As of today, the Company expects its cash runway to extend over three years based on currently planned development programs.
Conference Call
The R&D Day is scheduled to take place today from 10:00 a.m. to 12:30 p.m. ET in a virtual format. The call and accompanying slides will be webcast live on the Company’s website at https://investor.insmed.com/events. To listen to the conference call live, please dial (888) 317-6003 (domestic) or (412) 317-6061 (international) and reference conference ID number 0587949.
A replay of the conference call will be accessible approximately on hour after its completion through October 14, 2020 by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and referencing replay access code 10147009. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company’s website at https://investor.insmed.com/events.
About Insmed
Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product, ARIKAYCE® (amikacin liposome inhalation suspension), is the first and only therapy approved in the United States for the treatment of refractory Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. MAC lung disease is a chronic, debilitating condition that can cause severe and permanent lung damage. Insmed's earlier-stage clinical pipeline includes brensocatib, a novel oral reversible inhibitor of dipeptidyl peptidase 1 with therapeutic potential in non-cystic fibrosis bronchiectasis and other inflammatory diseases, and treprostinil palmitil inhalation powder, a treprostinil prodrug formulated as a dry powder for inhalation, which may offer a differentiated product profile for rare pulmonary disorders, including pulmonary arterial hypertension. For more information, visit www.insmed.com.
Forward-looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. "Forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of risks and uncertainties. Words herein such as "may," "will," "should," "could," "would," "expects," "plans," "anticipates," "believes," "estimates," "projects," "predicts," "intends," "potential," "continues," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) may identify forward-looking statements.
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The forward-looking statements in this press release are based upon the Company's current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timing discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following: failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside the U.S. or for the Company's product candidates in the U.S., Europe, Japan or other markets, including the United Kingdom as a result of its recent exit from the European Union; failure to successfully commercialize or maintain U.S. approval for ARIKAYCE, the Company's only approved product; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; impact of the novel coronavirus (COVID-19) pandemic and efforts to reduce its spread on the Company’s business, employees, including key personnel, patients, partners and suppliers; the risk that brensocatib does not prove effective or safe for patients in future clinical studies, including the ASPEN and STOP-COVID19 studies; uncertainties in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company's inability to obtain full approval of ARIKAYCE from the FDA, including the risk that the Company will not timely and successfully complete the study to validate a PRO tool and complete the confirmatory post-marketing study required for full approval of ARIKAYCE; inability of the Company, PARI Pharma GmbH (PARI) or the Company's other third party manufacturers to comply with regulatory requirements related to ARIKAYCE or the Lamira® Nebulizer System; the Company's inability to obtain adequate reimbursement from government or third-party payors for ARIKAYCE or acceptable prices for ARIKAYCE; development of unexpected safety or efficacy concerns related to ARIKAYCE; inaccuracies in the Company's estimates of the size of the potential markets for ARIKAYCE or its product candidates or in data the Company has used to identify physicians; expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; the Company's inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of ARIKAYCE or any of the Company’s product candidates that is approved in the future; failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; failure to successfully conduct future clinical trials for ARIKAYCE, brensocatib and the Company’s other product candidates, including due to the Company’s limited experience in conducting preclinical development activities and clinical trials necessary for regulatory approval and its inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval; risks that our clinical studies will be delayed or that serious side effects will be identified during drug development; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE or the Company's product candidates for commercial or clinical needs, to conduct the Company's clinical trials, or to comply with laws and regulations that impact the Company's business or agreements with the Company; the Company's inability to attract and retain key personnel or to effectively manage the Company's growth; the Company's inability to adapt to its highly competitive and changing environment; the Company's inability to adequately protect its intellectual property rights or prevent disclosure of its trade secrets and other proprietary information and costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on the Company by its agreements related to ARIKAYCE or the Company's product candidates, including its license agreements with PARI and AstraZeneca AB, and failure of the Company to comply with its obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; the Company's limited experience operating internationally; changes in laws and regulations applicable to the Company's business, including any pricing reform, and failure to comply with such laws and regulations; inability to repay the Company's existing indebtedness and uncertainties with respect to the Company's ability to access future capital; and delays in the execution of plans to build out an additional FDA-approved third-party manufacturing facility and unexpected expenses associated with those plan.
The Company may not actually achieve the results, plans, intentions or expectations indicated by the Company's forward-looking statements because, by their nature, forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. For additional information about the risks and uncertainties that may affect the Company's business, please see the factors discussed in Item 1A, "Risk Factors," in the Company's Annual Report on Form 10-K for the year ended December 31, 2019, the Company’s Quarterly Reports on Form 10-Q for the quarters ended March 31, 2020 and June 30, 2020 and any subsequent Company filings with the Securities and Exchange Commission (SEC).
The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date of this press release. The Company disclaims any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.
Contact:
Investors:
Argot Partners
Laura Perry or Heather Savelle
(212) 600-1902
Insmed@argotpartners.com
Media:
Mandy Fahey
Senior Director, Corporate Communications
Insmed
(732) 718-3621
amanda.fahey@insmed.com
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Exhibit 99.2
R&D DAYSeptember 30, 20201
AgendaSectionSpeakersWelcome & Kick-off Will Lewis Chair & Chief Executive OfficerTreprostinil Palmitil Inhalation Powder OpportunityDr. Eugene Sullivan, M.D. Chief Product Strategy Officer Dr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center Division of Cardiology Lead Investigator for Planned Phase 2a TrialBrensocatib Development Program UpdateDr. Kevin Mange, M.D., MSCE Head of Clinical Development Colleen Silk General Manager, BrensocatibARIKAYCE Front Line and Global Expansion UpdateDr. Kevin Mange, M.D., MSCE Head of Clinical Development Neil Hughes General Manager, Head of Europe, Middle East and Africa (EMEA) Commercial Roger Adsett Chief Operating OfficerFinancial Update Closing RemarksSara Bonstein Chief Financial OfficerQ&A Session Insmed Executive Team & Participants2
• • • Forward Looking StatementsThistation contains fotwatd.tooti,.$llltttnents that involvt- sutlstartiall rilob andties.. "kkfwarG-tooking b." as tflat termidtfint!d in tPrivate Stnritie Utigation Refonn Ad of 1995,. areu that art! not hGbOfical facts and k'l o olvt' a nutllbt!r of rills and uneertairtie. Words I!Nf!in as "mlfo/; .....,..... •should." •OCM.td; "would," •tllpt!(ts..• "plans; "an tidpa " •bt!lit!\aes,.• •tstifn&te," "prc;ects,: "predicn,." •intMcts; "pootentia• •continuea;nd sitnitw t? presions (awell as othef wordor t? preuions ting Mure ts.conditiOont sci'turnstances) trOf identify for\IW'¥'d.tooti,.statements. .. $tlllttnents in this pr r&arft! iobansed 1Jf1011 the Comf*'IYC'l WN!nt expectations and bt!liefs, and iJwol oe known and unknown rliob,. un:trtaintie and othef factol'l,. may autht! eotr.,an'(s adoal rtstJtis,. and athiew!mt!OU and Utmi itlg of ts todifftr materially frcm the l!s, perfonnanet', acfli ts or titning di$c:usst'd, projectf!d,. anticipated 01 indicattd in any forwarcHoot"tf18 statemt!nts. $U('h risks, I.W'!Ot!rtainties and Otllt!r factots indude, a.nong otlltn. tilt- foloM.:trisk that brt!nsocatib GoeJ not prefftocti oe or uie fot patitnts in the STQP.CO\I1Dl9 bulint!ss or «<notnit: disruptionsto catastro¢\es Ot otlltr NMU. ind udiog natonldiW stersor public htaJttl O"Ges; impact of the nowcor (COVII>19) panGt!mk and efforts to utt' its sprtad 01'1 OUt busintu, ttnployets, indudingPt'f'SOMd. patients, par1J'Iers and .w; faiiUI'f! to sucxts:Sfully commercialae or maintain U.S. approyal for ARIKAYCt", tht' Company'l OrfV appro..td product; uncertllintits in U*.gret- ol martttand m111keting inh'asb'ucture at to p¥ttter 110ith UW'd p¥ties that offer sucfl 11:n ir.f rastruc:ture f or diltribution of AIUKAYCE or any of tht! Comp3tly's candidates that is &ppro..td in tfle future;hirurt! toobt!i'l rtgulatorvapproy&l to expand ARIKA't'CE's indication to a tw'oaGt!r patient population; failure to suo::ts:Sfully confutdinical b'illlJ f or AIUKAYCE, brM$001tib and the Company'l odlt!r pr'Oduct caruldates,. ini'AI!Iins dut! to the Cornpr;;wly'l limited expt!rien:t- in conpreclinical deW! nt actillitit'$ and clinical tri&l$ llt!a'Ssar( f OI"u.gu Moy approval and tfle eotr.,&i?(s inability to tnroll or l'f!lllin suHicit!nt patients to c:onduct&nd compleott! utrill:I$or Sf!n«M:t! data nect':S$¥'( f or reg\.btorv appro11lll;riW tflal tht! eotr.,an'(s dinic&l studit!s will be delayt!d at that strious side effects wil bt! hk!ntifted during crrug de<.lelopment; failto obtain.or dt!ltrvs in obtainq, rtgulatorvapproy&l$fat ARICAVCE outstihe u.s. at for tht! an'(s product eandidMe: in tilt- U.S., C..oJapan C/1' otlltr m111keb,. i11C'hrding tilt- United Kir'lgdom as a result of its recent exit from the lin Unia; failure ol third parties ontht! Company is dept!illk!nt to m&nufed si.KII'ietlt quantities of ARIKAYCf at the Company'l candidates for C:OI'Mltl'ti&l or dinical nt!eds, to conduct tht! Ccmpany's dinkall trill:I'-or to v,ijt}J lawand tf!8utMiclns that impBd theCOf'r1)&n'(s busint':S$ at ments with t"""'lin'(; tflt! Companfs inalllflly to at1n1rt lind retain kper50Mel at to elftttNt!ly m111191Company's grcwtfl; tfle Company'l inability to &dapt to its hiSJIIy titNt! &nd t!IY.rironment; the Company'l liflly to ade(Jiately prot«t its i uaJ property riBJlts or prf!Yt!ntof its tradeand othtr poropor'i!otaty inf Ot"mation andexpt!(tatioM indicated by theCcmpany's forwarcHooking ts tlecause, bV thdr nature.forward-too-killiJ ts invrim andb«ause they relate to NMts and depend on drcumltanees that"*'!or fro( not ootul' in tfut n.fat addltion&l information &bout tflt! riSks andties that fro( llff«t tfle eotr.,&n'(s bucillt!U,. plt!atlfll!UitldiKUSStd in Item lA."Rilol llctol'l,." in tht! CompAnnual Report 01'1 form lO.K fat tfle yea. M*d r 31. 2019, Q.uarttrfo( Rt!ports 01'1 form 1()-Q for the quartttS M*d M!«h 31, 2020 and AJne lO, 2020.. &nd IIJ?fS UMt CompBny filtlgJ roith the soc.Tht! Company eai.Cions readt!rs not to pl&ce unGue l'f!lillnte on &ny such forward- l«tting .ltlltements, vA!ic::fl speat Oflly as ol the date ol this presentatim. The Company disclaitns any obtiglltitw,as $f!t:ifica!ly !Wed by 111w and the rol tfle SEC. to pub&ly update or reuai ny such .ltllttmMts to l'f!li&t &ny cfla,.in expt :tations 01' in nts.conditions Cl' drcumltlltiCt':S on vdiich &nV sucfl statements "*'! II!! bast!or that may alfect tht! litlelihood that actual rtsults'Aildiffer from thcbt'set forth in tfle forwatd.looti"S statements.IIC!Oefltanee of ARIKA't'CE by phv*iam. patitnts, tflird-p611y P'l'fOI"S and otflers in thecommunity; tht' Comp&ny'l inability to otJtain full approwll of ARIKAYCE from tOil. including trisk that tht' Company roill not timt!ly and SUCXts:Sfully oompl'the stucJ'( to validatt' a PAO tool and oomtht' 0011firmatorv pos:tof'llark!ti,. .m.v ruif!d fCI' full appnMI of ARIKAYCC; inability ol tht! Company, PARI or tht! Company'lotht'r third party manufat.burs to compfy v,ijtfl regutatorv rtquirtmMts rto ARIKAYCf or tlllmira• Nt!buliltr stht! eotr.,an'(s in&bility to obtain lldeq ut'St!me. from soutmmt!nt or third-f:larty payors f or AIUKAYCE or atteptable prices f or ARIKAYCC; dt!uelopment of u'llllttv 01' elf icatV OOIIC:ti'TI$ rto ARIKAYCE or brM b; ina0C:Ur11C:ies in tfle eotr.,al?(s e:tin'lflte of tflt! soi 1 tpotetti&l markets f or MIKA't'CE at its product candidates or in data the Company has u$t'd to i ntify pfly.licians; exrate of f*ient uptake, Guration of treatmt!nt, at ex p : titnt adi!Nf!nee or dGo:lntinuation rattht! eotr.,&i?(s in&bifity to CN!alt! 11n dh!ctiw directOC»tS aswith lltiption at othtr proa!tdif'lgJ relai:M to sucfl ; rtstriclion$ 01' othef obigations on UCompany by its gr ts rto ARIKAYCf or tCotnpai?(s product candidates. including its k:ense ll mt!nts v,(jtfl PARI lind As11a2Mtca Aa, lind failureof tfle Company tocompiV t/Oith its ob&g;Mions under sucflgr ts; tfle oe»t and potenti.W N!putational result ing frC/1'1'1iliglltion tollroflicfl theCcmpany isor maya f*tV, i11C'Iuding pr0l11uct btlffity dllims; Ueotr.,&n'(s lmittd eJCperietlte Opt!rllting irumation&ll)t; cflain Ia"" and r ns &pplicallle to tfle Company'$ bu$iness, ir'doldany pricirlg i'f!IOt"m, and flliiWto oompr:v with .M.ICh laws and rtgulations; i nallillty to repay tht! Company's exiW"S inddltedness and unoertainties ""ith repect to tilt- Cornpr;;wly'l abilty to &oe:eu futeapitat; and Gt!l:tyl in tfle tcution d plans to build out &n addilim&l fOA.·&pprO\Itd third- paf1V manufaorturi"S ladlity and u pedt!d expMse: asKidllttd 'Aith thoseTht! Compa.,.,. mav not ac.tuaty the reults., plans, intMtions or••••••••
Will Lewis Chair & CEOMission, Vision & Strategy4
Transformational Growth StrategyWorld Class TeamResearch & Development ExpertiseGlobal Commercial PresenceBusiness Development StrengthBrensocatib NCFBEPipeline TPIP Brensocatib expansionBrensocatib NCFBEARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE Refractory MACARIKAYCE Refractory MACARIKAYCE Refractory MACARIKAYCE Refractory MAC5
Dr. Eugene Sullivan, M.D. Chief Product Strategy OfficerDr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center Division of Cardiology Lead Investigator for Planned Phase 2a TrialTreprostinil Palmitil Development Update 7
Harnessing the Full Potential of the Prostanoid Pathway in Pulmonary Arterial Hypertension (PAH)Prostanoids have long been considered the cornerstone therapy for PAH but clinical use has faced challenges related to rapid metabolism and tolerability issuesTreprostinil palmitil has the potential to address the shortcomings of the existing prostanoid therapies by:• Potentially minimizing side effects, both local and systemic • Potentially maximizing the vasodilatory activity, by maintaining high local concentrations in the lung • Allowing for histologic disease-modifying effects of prostanoid therapy8
Agenda1 Pulmonary Arterial Hypertension (PAH)2 Treprostinil Palmitil Inhalation Powder (TPIP)3 Highlights of Preclinical Data4 Product Differentiation5 Path Forward9
Dr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center Division of Cardiology Lead Investigator Planned Phase 2a TrialPulmonary Arterial Hypertension (PAH) Treatment Landscape10
Types of Pulmonary Hypertension11
Types of Pulmonary HypertensionLung disease/hypoxiaLeft-sided heart disease12
Types of Pulmonary HypertensionLung disease/hypoxiaThromboembolic diseaseLeft-sided heart disease13
Types of Pulmonary HypertensionThromboembolic diseaseIPAH and APAHLung disease/hypoxiaLeft-sided heart disease14
Pulmonary Hypertension: Diagnostic classificationPulmonary arterial hypertension (PAH)1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, ENG, SMAD9, CAV1, KCNK3 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infectionPH due to Lung Diseases and/or Hypoxemia3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4. Sleep-disordered breathing 3.5. Alveolar hypoventilation disorders 3.6. Chronic exposure to high altitude 3.7. Developmental abnormalities1.4.3. Portal hypertension 1.4.4. Congenital heart diseases 1.4.5. Schistosomiasis 1’ Pulmonary veno-occlusive disease and / or pulmonary capillary hemangiomatosis 1’ Persistent pulmonary hypertension of the newbornPulmonary hypertension due to left heart disease2.1. Left ventricular systolic dysfunction 2.2. Left ventricular diastolic dysfunction 2.3. Valvular disease 2.4. Congenital/acquired left heart inflow/ outflow tract obstruction and congenital cardiomyopathiesChronic thromboembolic pulmonary hypertension (CTEPH)Pulmonary hypertension with unclear multifactorial mechanisms5.1. Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy 5.2. Systemic disorders: sarcoidosis, pulmonary histiocytosis: lymphangioleiomyomatosis 5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH15
Pulmonary Hypertension: Diagnostic classificationPulmonary arterial hypertension (PAH)1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, ENG, SMAD9, CAV1, KCNK3 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infectionPH due to Lung Diseases and/or Hypoxemia3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4. Sleep-disordered breathing 3.5. Alveolar hypoventilation disorders 3.6. Chronic exposure to high altitude 3.7. Developmental abnormalities1.4.3. Portal hypertension 1.4.4. Congenital heart diseases 1.4.5. Schistosomiasis 1’ Pulmonary veno-occlusive disease and / or pulmonary capillary hemangiomatosis 1’ Persistent pulmonary hypertension of the newbornPulmonary hypertension due to left heart disease2.1. Left ventricular systolic dysfunction 2.2. Left ventricular diastolic dysfunction 2.3. Valvular disease 2.4. Congenital/acquired left heart inflow/ outflow tract obstruction and congenital cardiomyopathiesChronic thromboembolic pulmonary hypertension (CTEPH)Pulmonary hypertension with unclear multifactorial mechanisms5.1. Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy 5.2. Systemic disorders: sarcoidosis, pulmonary histiocytosis: lymphangioleiomyomatosis 5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH16
2-year mortality untreated = 50%**D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991;115:343–349.17
Progression of RV DysfunctionChampion HC, Michelakis ED, Hassoun PM. Circulation 2009;120:992-100718
History, symptoms,sogns and/or laboratory tests suggestove of PHAssess probaboloty of PHEchocardiographoc probabolity of PH'Lowldentofy hogh-nsk patoentsFast-track referralof selected patientsHigh or ontermedoateConsider V/Q scan to screen for CTEPH•Consider other causes and/or follow-up•Doagnose common causes of PH V/0 scan abnormalDoagnose rare causes of PHConsoder left heart dosease (assess pre-test probabolotyland lung doscase§No clonocally sognifocant left heart dosease orRefer to PH expert centre!
History, symptoms,sogns and/or laboratory tests suggestove of PHAssess probaboloty of PHEchocardiographoc probabolity Low of PH'ldentofy hogh-nsk patoentsFast-track referralof selected patientsHigh or ontermedoateConsider V/Q scan to screen for CTEPH•Consider other causes and/or follow-up•Doagnose common causes of PH V/0 scan abnormalDoagnose rare causes of PHConsoder left heart dosease (assess pre-test probabolotyland lung doscase§No clonocally sognifocant left heart dosease orRefer to PH expert centre!
Algorithm for the diagnosis of PH and its causes (cont)/ Management at PH expert centreICTEPH doagnostoe)+Any m smatched -Review orNormalperfuSIOnalgonthm perlusoon defectperform f--.scan•PH not PH not confirmed Consoder other confirmed! M ttomodabty d1.1gnoshc assessment l RHC for PH doagno'' and haemodynam ,causes1 chara'trlf'IS..lhonPH conformedCTEPH not confirmed Revoew by muttod scoptonary PH team• I Monitor andCTEPH confirmedl l \ss PH ctassolocatoonessI RHC·Right Heart Catheterization IPH classoloedll Approproatenot certamConsoder troat oltreatment treatment'
Algorithm for the diagnosis of PH and its causes (cont)/ Management at PH expert centreICTEPH doagnostoe)+Any m smatched -Review orNormalperfuSIOnalgonthm perlusoon defectperform f--.scan•! M ttomodabty d1.1gnoshc assessment+PH notPHn RHC for PH doagno''confirmed Consoder other confirm d and haemodynarn , causes1 ct)ara'trlf'IS..lhonPH conformedCTEPH not confirmed Revoew by muttod scoptonary PH team•"""'I Monitor andCTEPH confirmedPH classoloedll\ss PH ctassolocatoon not certamessI RHC·Right Heart Catheterization IApproproateConsoder troat oltreatment treatment'
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonists21
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonists21
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonistsParenteral prostanoids are recommended as first- line therapy for FC IV patients and FC II and III patients with rapid progression. Inhaled prostanoids are recommended for indicated patients unwilling or unable to manage parenteral prostanoids, or as second-line alternatives for patients who are uncontrolled on ERAs or PDE5s (alone or in combination).21
PAH Treatments – Approved TherapiesSpecific PAH agentsProstacyclin Analogues• epoprostenol (IV)• iloprost (inh)• treprostinil (IV, SQ, inh, po)• selexipag (po)Endothelin antagonists• bosentan (po)• ambrisentan (po)• macitentan (po)PDE-5 inhibitors• sildenafil (po)• tadalafil (po)Soluble gunalylate cyclase agonist• riociguat (po)26
Prostacyclin Advantages and Trade-OffsAdministration Advantage LimitationsOral Convenient • GI side effects limitSystemically administered prostanoids (oral or parenteral) are limited by the side effects:Parenteral EffectiveInhaled Targeteddosing• Systemic toxicities limit dosing • Site pain, infection, inconvenience• Short treatment effect requires multiple administrations per day • Sawtooth PK/PD profile• Hypotension • Nausea/vomiting • Diarrhea • Headache• Flushing • Jaw pain27
Prostacyclin Advantages and Trade-OffsAdministration Advantage LimitationsOral Convenient • GI side effects limitSystemically administered prostanoids (oral or parenteral) are limited by the side effects:Parenteral EffectiveInhaled Targeteddosing• Systemic toxicities limit dosing • Site pain, infection, inconvenience• Short treatment effect requires multiple administrations per day • Sawtooth PK/PD profile• Hypotension • Nausea/vomiting • Diarrhea • Headache• Flushing • Jaw painGoal for a new prostanoid therapy: convenient administration; sustained, high lung concentration; lower systemic exposures; potential for anti-proliferative, disease-modifying effects.28
A Poten Differentiated Prostanoid 29
Treprostinil Palmitil Inhalation Powder (TPIP)• TPIP is a dry powder formulation of treprostinil prodrug, treprostinil palmitil*• The dry powder inhaler (DPI) device is the Plastiape RS01 capsule- based deviceTreprostinil Palmitil(INS1009)Lung Esterase• Once delivered to the lung, treprostinil palmitil is hydrolyzed by endogenous esterases to active treprostinil*Previously treprostinil palmitil was formulated as a nebulized suspension (TPIS).C16-OHTreprostinil30
Highlights of Preclinical Data 3
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)32
Highlights of Preclinical DataPotential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)33
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilOnce-or-twice-daily administrationEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)34
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Comparable effects at lower systemic exposuresImproved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)35
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilPotential disease modifying activityEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)36
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilPotential Improved TolerabilityEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)37
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)38
Improved Pharmacokinetics: Prolonged Lung Residence, Lower Cmax, Prolonged Half Life (Rat and Dog)RAT Lung and Plasma LevelsDOG Plasma Levels100001000100Treprostinil Palmitil 42 μg/kg Treprostinil Palmitil 108 μg/kg Treprostinil 215 μg/kg ExtrapTreprostinil PalmitilInhaled TP Inhaled TPInhaled TP Inhaled TPTreprostinil Palmitil1010.1Treprostinil0.010 5 10 15 20 25 Time (h)10X CmaxTreprostinilTreprostinil PalmitilTreprostinilF.G. Leifer et al. (2018) Drug Res 68: 1-10M. R. Corboz, et al. (2017) J. Pharmacol. Exp. Ther. 363:348–357. 39
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)40
Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog, Hypoxic Challenge)6 g/kg 23g/kg 57g/kg 0 138 g/kg-2-4-6-8-10-12Nose only inhalation; doses are those presented to the animals (lung dose is 1/10 of the values shown)0 2 4 6 8 10 12 14 16 18 20 22 24Time Post Dose (h)Data on file, Insmed Inc.41
Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog, Hypoxic Challenge)1614121086420Dose g/kg80.93522.3102.7Average right ventricular pulse pressure (RVPP) response to hypoxia challenge in two dogs following inhalation of different doses of TP; the ‘wash out’ period between doses was ≥7days. Shown at t=0 is the no-treatment baseline average (values were taken before dosing).-2 0 5 10 15 20 25 Time after dosing (h)Data on file, Insmed Inc. 42
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)43
Local Pharmacodynamic Effect Pulmonary Vasodilator Activity at Significantly80PBS 60 infused40200IV TreprostinilLower Plasma Treprostinil Concentrations (Rat)0.0001 0.01 0.1 1 10 10060 xRats challenged with the thromboxane mimetic U4661980PBS 60 inhaled40Inhaled Treprostinil Palmitil200 0.0001 0.01 0.1 1 10 100Plasma Treprostinil (ng/mL)Chapman et al. (2018). Inhaled hexadecyl-treprostinil provides pulmonary vasodilator activity at significantly lower plasma concentrations than infused treprostinil. Pulm. Pharmacol. Ther. 49: 104-111. 44
Local Pharmacodynamic Effect Pulmonary Vasodilator Activity at Significantly Lower Plasma Treprostinil Concentrations (Dog)Telemetered Dogs (Hypoxia Challenge)25PBS 20 infused15Inhaled Treprostinil PalmitilIV TreprostinilEC50 value: TP 550x lower than IV TRE10PBS 5 inhaled0-5 0.0001 0.001 0.01 0.1 1 10 100Chapman et al. (2018). Inhaled hexadecyl-treprostinil provides pulmonary vasodilator activity atPlasma TRE (ng/mL)significantly lower plasma concentrations than infused treprostinil. Pulm. Pharmacol. Ther. 49: 104-111.45
Local Pharmacodynamic Effect Continuously Inhaled vs. Continuously Infused (IV) Treprostinil in Sheep…prostacyclin analogs are more potent pulmonary vasodilators when delivered by aerosol than when given intravenously. Systemic hemodynamic effects are also minimized by aerosol administration of the drug, making this approach especially appealing. Duration of action of prostacyclin is short, requiring an unrealistic frequency of administration for clinical use (6, 33), but development of analogs (e.g., treprostinil) or formulations that are long acting could make this approach feasible.”“We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.46
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostinil“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)47
Treprostinil Palmitil Inhalation Solution Improved Both Hemodynamics and Vascular Remodeling in the Rat Sugen-HypoxiaModel of PAHImproves Pulmonary Arterial PressureReduces Wall Thickening* significantly different from the naïve group# significantly different from the vehicle group1Fulton Index is a commonlyTreprostinil Palmitil†NaïveVehicleTreprostinil Palmitil†used quantitative measure of the degree of right ventricularImproves Fulton Index1 Reduces Vessel ObliterationsMuscular Semi-muscular Non muscularhypertrophy Am. J. Res. Crit. Care Med. 2020: 201, A2094. Poster was not presented due to COVID19. Data on file, Insmed Inc.100 90 80 70 60 50 40 30 20 10 0*** # #Data on file, Insmed Inc. †Pulmonary dosesTreprostinil Palmitil†NCaïtvr eVNeehgicClter 2ug/kg INS 1009 6ug/kg INS 1009 Treprostinil Palmitil† 48
TPIP Demonstrated Superior Effect on PA Pressure and RV Hypertrophy in the Rat Sugen-Hypoxia Model of PAHPulmonary Arterial Pressure 50 *40 *0.8Fulton Index1* * * **30 * * ## 20* # ** #0.60.4* * *#0.2 100 Nx VehicleTPIP 59 µg/kgTPIP (QD)TPIP 117 µg/kgVehicle TRE 65 µg/kgNebulized TRE (QID)Vehicle TRE 810 ng/kg/minIV TREVehicle Selexipag 30 mg/kgOral Selexipag (BID)0.0Nx Vehicle TPIP 59 µg/kgTPIP (QD)TPIP 117 µg/kgVehicle TRE 65 µg/kgNebulized TRE (QID)Vehicle TRE 810 ng/kg/minIV TREVehicle Selexipag 30 mg/kgOral Selexipag (BID)* significantly different from Normoxic control (Nx) # significantly different from Vehicle Group 1Fulton Index is a commonly used quantitative measure of the degree of right ventricular hypertrophy: it is the weight ratio o f right ventricle/(left ventricle + septum)Data on file, Insmed Inc. 49
TPIP Demonstrated Superior Effect on Vascular Remodeling in the Sugen-Hypoxia Rat Model of PAHWall Thickness ���� ���� ���� − ��� ������� ���� ������ % = 40���� ���� ����× ���***30 #***##******#******##1009080Non muscular Semi-muscular Muscular*** *20100* 706050403020 ***10 *** 0##***### ***### ***### *********# ***#*********# ***# *********###***### ***NormoxicVehicle59 µg/kg117 µg/kgVehicle65 µg/kgVehicle IV810Vehicle30 mg/kgNormoxicVehicle59 µg/kg117 µg/kg Vehicle Neb65 µg/kgVehicle IV810Vehicle30 mg/kgcontrol (n = TPIP (n =TPIP (n =TPIP (n =Neb TRENeb TRE TRE (n = 7) ng/kg/minSelexipagSelexipagcontrol (n = TPIP (n = 9)TPIP (n =TPIP (n =TRE (n = 6) Neb TRE (nTREng/kg/minSelexipagSelexipag8) 9)11)10)(n = 6)(n = 10)IV TRE (n = 6)(n = 7)(n = 9)8) 11)10)= 10)IV TRE(n = 7)(n = 9)Data on file, Insmed Inc.* significantly different from Normoxic control group # significantly different from Vehicle group* and # p <0.05 ** and ## p < 0.01 *** and ### p < 0.001 50
TPIP at High Dose Shows Superior Effect Overall in the Sugen-Hypoxia Rat Model for PAHParameter value = (Value – Value of Normal) / (Value of Vehicle – Value of Normal)Data on file, Insmed Inc. 51
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2Prolonged duration of pharmacodynamic activity“Local” pharmacodynamic effect• Achieves the same pharmacodynamic (vasodilatory) effect at significantly lower systemic concentrations, compared with IV treprostinilEffect on hallmark histopathologic features in the sugen/hypoxia model• Remodeling effect, superior to other prostanoidsReduced incidence of cough (guinea pig model)52
Reduced Incidence of Cough Threshold to Induce Cough Increased 7-Fold (guinea pig model)80 80 * 60 * 6040 40 * * 20 200 0TRE7 X HigherTPIP ***Significantly different from vehicle. **Treprostinil molar equivalent doses; TP doses are 2.3, 12.8 and 35.8 g/kg. Data on file, Insmed Inc.53
Product Differentiation 54
Treprostinil Palmitil Inhalation Solution Phase 1 StudyPlasma PK in Healthy VolunteersTreprostinil Plasma PK SummaryTyvasoTPIS 85o Substantially lower Cmax than Tyvaso®o Persistent plasma levelsCohort 1 (n = 6)TPIS 85 µgTyvaso 54 µgof drug beyond 12 hours consistent withCmax (ng/mL) 0.089 0.958AUC0-24 (ng*h/mL) 0.614 0.872Tmax (h) 1.02 0.258T1/2 (h) 5.69 0.485Time Since Dose (h)sustained releaseHan et al. (2016) Single-Dose Pharmacokinetics of C16TR for Inhalation (INS1009) vs Treprostinil Inhalation Solution. ERS International Congress, September 3-7, London, United Kingdom, abs 3505 (poster PA2303).55
Treprostinil Palmitil Inhalation Powder (TPIP) a Potentially Differentiated ProstanoidConvenience: portable, dry powder inhalerIf the characteristics suggested by the preclinical studies are borne out in the clinical development program, TPIP could represent a differentiated productQD or BID dosing (prolonged lung residence time, prolonged half life, prolonged duration of pharmacodynamic activity)Improved safety/tolerability • Systemic tolerability (lower Cmax) • Local tolerability (reduced cough)Greater vasodilatory pharmacodynamic effect at lower systemic exposures (sustained lung residence time takes advantage of the local effect seen in multiple animal models)Potential disease modifier – may be able to benefit the histopathologic process, whereas Tyvaso, due to transient local exposure, cannot56
Treprostinil Palmitil Inhalation Powder (TPIP) a Potentially Differentiated ProstanoidConvenience: portable, dry powder inhalerIf the characteristics suggested by the preclinical studies are borne out in the clinical development program, TPIP could represent a differentiated productQD or BID dosing (prolonged lung residence time, prolonged half life, prolonged duration of pharmacodynamic activity)Improved safety/tolerability • Systemic tolerability (lower Cmax) • Local tolerability (reduced cough)Greater vasodilatory pharmacodynamic effect at lower systemic exposures (sustained lung residence time takes advantage of the local effect seen in multiple animal models)Potential disease modifier – may be able to benefit the histopathologic process, whereas Tyvaso, due to transient local exposure, cannot56
Next Steps for TPIP DevelopmentPhase 1 UnderwaySAD/MAD StudyObjective Establish PK and tolerability profileTop line results expected in Q1 2021Initiate Phase 2a in Early 2021Exploratory, single dose studyObjective Demonstrate proof of mechanism, understand PK/PD relationship, confirm tolerabilityResults expected in 2021Initiate Phase 2b in H2 2021Objective Demonstrate hemodynamic effect size, inform design for pivotal program58
Next Steps for TPIP DevelopmentPhase 1 UnderwaySAD/MAD StudyObjective Establish PK and tolerability profileTop line results expected in Q1 2021Initiate Phase 2a in Early 2021Exploratory, single dose studyObjective Demonstrate proof of mechanism, understand PK/PD relationship, confirm tolerabilityResults expected in 2021Initiate Phase 2b in H2 2021Objective Demonstrate hemodynamic effect size, inform design for pivotal program58
Brensocatib NCFBE to Serve as ‘Launch Pad’ for Neutrophil-mediated PortfolioSerious Unmet Need Conditions• Cystic Fibrosis • Granulomatosis with Polyangiitis • Apha-1 Antitrypsin DeficiencyNCFBE Program WILLOW + ASPENLarger MarketsResearch Pipeline• Inflammatory Bowel Disease* • Rheumatoid Arthritis* • Lupus Nephritis* • COPD/Asthma† • Oncology• External collaborations • Insmed expertiseNCFBE, non-CF bronchiectasis * Preclinical data generated †AstraZeneca has exercised its option to develop brensocatib in COPD & asthma through Phase 2b. Further development subject to agreement on commercial terms with Insmed. 60
Brensocatib Clinical Development 61
Bronchiectasis: Pathogenesis Bronchiectasis Vicious Cycle*INFLAMMATIONPersistent inflammatory response, causing lung damageBACTERIAL COLONIZATIONIncreased susceptibility to chronic bacterial infection and colonizationAIRWAY DESTRUCTION ABNORMAL MUCOCILIARY CLEARANCEAn environmental insult or disease process leads to bronchial wall destruction and dilationStructural damage impairs protective mucociliary clearance* All references to bronchiectasis related to our WILLOW and ASPEN clinical studies, potential launch of brensocatib and global prevalence refer to non-cystic fibrosis bronchiectasis. 62
WILLOW Study Results Underscore Potential of Brensocatib63
Brensocatib Phase 2 WILLOW Study Design6 weeksScreeningStratified by Pseudomonas1:1:1Treatment period 24 weeksBrensocatib 25 mg QD Brensocatib 10 mg QD Placebo QDOff treatment 4 weeks• Primary objective:• Time to first exacerbation over 24 weeks in patients with non-cystic fibrosis bronchiectasis (NCFBE)• Secondary objectives:• Pulmonary exacerbation rate over 24 weeks• Change in QOL-Bronchiectasis questionnaire respiratory symptoms domain over 24 weeksaeruginosa on sputum culture and use of macrolidesBaseline day 1 randomizationClinic visits day 1, week 2, week 4, 8, 12, 16, 20 and 24/EOTEOT day 169EOS day 197 ± 3• Change in post-bronchodilator ppFEV1 over 24 weeks• Change in sputum NE activity from pretreatment to on-treatmentEOS, end of study; EOT, end of treatment; NE, neutrophil elastase; ppFEV1, percent predicted forced expiratory volume in 1 second; QD, once daily. Phase 2 WILLOW Study: NCT0321891764
25 mg brensocatib vs. placeboRate of Exacerbations by Patient Subgroups10 mg brensocatib vs. placeboChalmers et al, ERS International Congress 2020, 7-9 September. RCT4135 BSI, bronchiectasis severity index; FEV1, forced expiratory volume in 1 second aBulgaria/Poland65
Dose Response Effect Seen Consistently Across Sputum Neutrophil Serine Proteases (NSPs) Mean (SE) Change from Baseline to Week 24 (log10 [mg/mL])Neutrophil ElastaseProteinase 3 Cathepsin GChalmers et al, ERS International Congress 2020, 7-9 September. RCT4135 66
WILLOW Safety Datano. (%) Placebo (n=85)Brensocatib 10 mg (n=81)Brensocatib 25 mg (n=89)TEAE resulting in study discontinuation 3 (3.5) 3 (3.7) 4 (5.5) TEAE resulting in treatment discontinuation 9 (10.6) 6 (7.4) 6 (6.7) Serious TEAE19 (22.4) 11 13.6) 10 (11.2) Serious TEAEs in ≥ 3% of patients in any groupInfective exacerbation of bronchiectasis 9 (10.6) 5 (6.2) 4 (4.5) Pneumonia3 (3.5) 0 4 (4.5) Any TEAE 67 (78.8) 75 (92.6) 74 (83.1)TEAEs in ≥ 10% of patients in any groupCough 10 (11.8) 15 (18.5) 12 (13.5) Headache3 (3.5) 8 (9.9) 12 (13.5) Sputum increased6 (7.1) 9 (11.1) 9 (10.1) Dyspnea2 (2.4) 3 (3.7) 9 (10.1) Infective exacerbation of bronchiectasis 9 (10.6) 5 (6.2) 4 (4.5)Diarrhea 9 (10.6) 5 (6.2) 3 (3.4) 67
Brensocatib Phase 3 Development Program 68
ASPEN Study: Single Trial Designed to Support Global FilingBreakthrough Therapy Designation for brensocatib in non-cystic fibrosis bronchiectasis (NCFBE)Robust efficacy endpoints, supported by WILLOW resultsIntegrates feedback from Health Authorities69
ASPEN Phase 3 Study DesignPrimary Endpoint:Treatment periodOff treatment• Rate of pulmonary exacerbations over the 52-week treatment periodKey Secondary Endpoints:• Time to first pulmonary exacerbation over the 52-week treatment period• Proportion of subjects who remain exacerbation-free over the 52-week treatment period• Change in FEV1Powered at 90% to detect 30%Up to 6 weeksScreeningStratified by:• Geographic region• Pseudomonas1:1:152 weeksBrensocatib 25 mg QD N=540Brensocatib 10 mg QD N=540Placebo QD N=5404 weeksreduction in exacerbation rate• Type I error: 0.01 (two-sided)• P-value = less than 0.01aeruginosa on sputum culture• Number of prior PEs (2, or ≥3) in previous 12 monthsBaseline day 1 randomizationClinic visits week 4, 16, 28, 40, 52 (EOT) and 56 (EOS)Phone visits week 10, 22, 34 and 46EOT day 364EOS day 392EOS, end of study; EOT, end of treatment; FEV1, forced expiratory volume in 1 second; QD, once daily; PE, pulmonary exacerbation 70
ASPEN Timeline Considerations36 Countries~480 sites6 Fast Track CountriesTargeting WILLOW study sites71
Brensocatib Commercial Outlook 72
Brensocatib Strategy Builds on Successful First Launch in NCFBEN Phase 3 trial for non-cystic fibrosis onchiectasis (NCFBE)Prepare for successful global launch in NCFBEAdvance clinical programs for cystic fibrosisaluate other neutrophil-modulated eases for future research & label xpansion73
An Approved NCFBE Treatment to Reduce ExacerbationsCould Address Unmet Needs Across StakeholdersPatients HealthcarePayers“It’s like waiting for• Symptoms of cough, dyspnea, fatigue interfere with daily life• Fear of exacerbations negatively impacts emotional and social well-being• Frustrated with time- consuming therapies that are not specific to BEProviders• Lack of efficacious anti- inflammatory option• Treatments that improve patient QOL and prevent exacerbations seen as largest unmet need• Recognize current treatments lack BE-specific clinical trial data• Treatment option with BE indication, greater efficacy, and reduction in exacerbations seen as unmet needsa hurricane – there’s a constant level of fear and anxiety of the unknown. When will an exacerbation hit? - BRONCHIECTASIS PATIE”NT74
Bronchiectasis is a Globally Prevalent Disease
Current Prevalence Estimates May Underestimate Global Patient Population, Given Underdiagnosis of NCFBECOPDBEAsthmaBetween 650K – 9M COPD patients in the US (4%1- 54%2) may also have NCFBEBetween 450K – 675K asthma patients in the US (2%-3%3) may also have NCFBE1. Agusti, A., Calverley, P.M., Celli, B. et al. Characterisation of COPD heterogenecity in the ECLIPSE cohort. Respir Res. 2010; 11: 122 2. Ni, Y., Shi, G., Yu, Y. et al. Clinical characteristics of patients with chronic obstructive pulmonary disease with co-morbid bronchiectasis: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015; 10: 1465–1475 3. Kang HR, Choi GS, Park SJ, et al. The effects of bronchiectasis on asthma exacerbation. Tuberc Respir Dis (Seoul). 2014;77(5):209‐214. 76
Well Positioned to Support a Successful Global Launch in NCFBEUniquely positioned to commercialize brensocatib, if approved, given theWell-developed US launch capabilities with ARIKAYCEExperience with patient finding and activationsynergies that exist between NCFBE and NTM lung diseaseGeographic and target HCP overlap with current US Sales structureEU/Japan teams mobilized for launch successAdvocacy and patient support77
Brensocatib Additional Opportunities 78
Strategy to Build a Neutrophil-mediated PortfolioSerious Unmet Need Conditions• Cystic Fibrosis • Granulomatosis with Polyangiitis • Apha-1 Antitrypsin DeficiencyNCFBE ProgramLarger MarketsResearch Pipeline• Inflammatory Bowel Disease* • Rheumatoid Arthritis* • Lupus Nephritis* • COPD/Asthma† • Oncology• External collaborations • Insmed expertise* Preclinical data generated †AstraZeneca has exercised its option to develop brensocatib in COPD & asthma through Phase 2b. Further development subject to agreement on commercial terms with Insmed. 79
Cystic Fibrosis GPACystic Fibrosis and GPA Identified for Further Clinical DevelopmentMOA ApplicabilityValue PropositionProviding a Roadmap for Development from CF to GPAClear role for neutrophils and NE in CF; Chronic bacterial infections of CF are neutrophil-mediated, and very elevated neutrophil counts in sputum are seen in CF patientsPotential to fill a need for CF-specific anti- inflammatory therapy, a category not currently met by marketed productsAn important additive therapy (on top of CFTR modulators) for CF patients who experience any pulmonary exacerbationsPreviously approved products (CFTR modulators) and support from the CF Foundation Therapeutics Development NetworkTwo distinct MOAs could be applicable: (1) Inhibits activity of NSPs, (2) Reduces expression of membrane-bound PR3Potential for additional treatment option for GPA patients during induction for a more efficacious response, or as an alternative option for sustained remissionPreviously approved product (Rituxan) and phase 3 development of avacopan80
Ongoing Investigator-Sponsored Clinical Study for Treatment of Severe COVID-19 InfectionsCould brensocatib be used to treat COVID-19?Currently under investigation in multi-site UK investigator-initiated research (IIR) studyDouble-blind, prospective, placebo-controlled, randomized trialUp to 300 patients; 10 sitesLed by University of Dundee’s Professor James Chalmers, MBChB, Ph.D.Prioritized by UK’s National Institute for Health ResearchPotential Data read-out: H1 202181
Kevin C. Mange, M.D., MSCE SVP, Clinical DevelopmentNeil Hughes General Manager, Head of EMEARoger Adsett Chief Operating OfficerARIKAYCENot for promotional use 82
Kevin C. Mange, M.D., MSCE SVP, Clinical DevelopmentARIKAYCEFront Line Program 83 Not for promotional use 83
ARIKAYCE® (amikacin liposomal inhalation suspension) Indication and Use• LIMITED POPULATION: ARIKAYCE is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.• This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.• Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.Not for promotional use 84
First-in-Disease Therapy for MAC Lung DiseaseMAC lung disease is a rare, progressive, and chronic condition that can cause severe, permanent damage to the lungsSymptoms often worsen over time, including chronic cough, dyspnea, fatigue, fever, weight loss, and chest painARIKAYCENovel, inhaled, once- daily formulation of liposomal amikacin taken with a nebulizerce™ liposomal technology delivers drug directly to the lungsProlongs release of amikacin in the lungs while limiting systemic exposureCaused by bacteria in the environment and is more likely to affect those with a history of lung conditions, like bronchiectasis or COPDComplementary portfolio Meaningful overlap in patient populations, with over 60% of bronchiectasis patients also having an NTM infectionNot for promotional use 85
ARIKAYCE Front Line Indication – Trial SummaryARISE (INS-415)Psychometric validation studySubjects: 100Start: Q4 2020ENCORE (INS-416)Double-blind PMR trialSubjects: 250Start: Q4 202086 Not for promotional use 86
Front Line Indication Registration ProgramScreeningARISEARIKAYCE + AZI* + ETH*ARISEPrimary Objective Demonstrate reliability, validity and responsiveness of the PRO/symptom scoresSecondary Objective Demonstrate effect of ARIKAYCE on culture conversion, time to cultureAdults with newPsychometricR Months 1-6Off Treatment**conversionMAC lung infectionValidation Study Month 7Placebo + AZI +ETHKey EndpointsAdults with new MAC lung infectionENCOREDouble-Blind R Registration PMR TrialARIKAYCE + AZI* + ETH*Months 1- 12Placebo + AZI + ETHKey Endpoints Month 13Off Treatment**Culture Negativity Endpoint Month 15ENCOREPrimary Endpoint Change from Baseline to Month 13 (one month off treatment) in respiratory symptom scoreKey Secondary Endpoint Proportion of subjects achieving durable culture conversion at Month 15 (3 months off treatment)*Azithromycin (AZI), Ethambutol (ETH) **Patients will be enrolled into separate open label extension studyhttps://clinicaltrials.gov/ct2/show/NCT03672630 Not for promotional use 87
Developing a Symptom Score for Front Line Indication Leveraging Existing Instruments to Expedite WorkRespiratory Symptom ScoreQuality of Life- Bronchiectasis (QoL-B) Patient Reported Outcome (PRO) QuestionnaireFatigue Symptom ScorePROMIS-Fatigue Short Form 7a QuestionnaireIn general, FDA requires description (validation) of questionnaires (PROs) to be used to support efficacy in the context of use (population of interest)Completed Concept Elicitation work with 25 patients with newly diagnosed MAC diseaseSupports specific questions in respiratory domain in QoL-B, and in PROMIS-Fatigue are meaningful / understandable to these patients and are likely the basis of computing symptom scores pending completion of Cognitive Interview work later this year.Not for promotional use 88
Developing a Symptom Score for Front Line Indication Lessons Learned from Prior Drug Development ProgramsDescribing longitudinal properties of questionnaires / PROs is required by FDA, in generalGlobal Blood Therapeutics incorporated describing longitudinal properties into Phase 3 study (HOPE study) for their new PRO in sickle cell diseaseARISE & ENCORE will evaluate symptom scores and other endpoints after completion of three-drug treatment regimen vs two-drug treatment regimenARISE will evaluate longitudinal properties as a separate study that will complete while ENCORE is enrolling• Provides for ability to adjust what/how items are used to compute final version of symptom scores in ENCORE while preserving integrity of ENCORENot for promotional use 89
Neil Hughes General Manager, Head of EMEAARIKAYCEEU Launch UpdateNot for promotional use 90
ARIKAYCE a Blueprint for Future Success2019 $136M net salesQ2 2020 $42.5MEngaged HCP & patient populationPositive reimbursement trends• Engaged healthcare providers• Educated patient population• Focus on payers to ensure reimbursementNot for promotional useARIKAYCE was one of the Top 10 most successful non-oncology rare disease launchesWe plan to repeat history with our growing pipeline91
ARIKAYCE Added to International Treatment Guidelines for Treatment of MAC Lung DiseaseGuidelines are a globally recognized standard for the prevention, diagnosis and treatment of NTM lung diseaseAddition of ARIKAYCE to new standard treatment regimen for adult patients with limited or no treatment options who failed to convert to a negative sputum culture after at least six months of treatmentTreatment should be continued for 12 months after culture conversionNot for promotional use 92
ARIKAYCE Added to International Treatment Guidelines for Treatment of MAC Lung DiseaseGuidelines are a globally recognized standard for the prevention, diagnosis and treatment of NTM lung diseaseAddition of ARIKAYCE to new standard treatment regimen for adult patients with limited or no treatment options who failed to convert to a negative sputum culture after at least six months of treatmentTreatment should be continued for 12 months after culture conversionNot for promotional use 92
Commercial Approach Meaningful Opportunity in EuropeUS~12K – 17K total refractory MAC patients (2019E)*~80K – 90K total diagnosed NTM patients (2019E)*EU5†~1,400 total refractory MAC patients (2018E)*~14K total diagnosed NTM patients (2018E)*Japan~15K – 18K total refractory MAC patients (2018E)*~125K - 145K total diagnosed NTM patients (2018E)**Source: Internal analysis of published NTM epidemiology, primary market research with treating HCPs, and anonymized patient level claims data in US † EU5 comprised of France, Germany, Italy, Spain and the United Kingdom94 Not for promotional use
ARIKAYCE Received Positive CHMP Opinion July 24, 2020Committee for Medicinal Products for Human Use (CHMP)of the European Medicines Agency has adopted a positive opinion recommending ARIKAYCE for the treatment of NTM lung infections caused by MAC in non- CF Patients with limited treatment optionsNot for promotional use 95
Prevalence of NTM in EU May be Greater Than Previously Reported…while anticipated EU indication slightly wider than only refractory MACNot for promotional use 96
EU Launch StrategyStrong but Lean InfrastructureSupport value, pricing & accessInsmed launch readinessIdentify and improve NTM lung disease treatment ecosystemsSupport for patients and HCPs for ARIKAYCE initiationOperational Excellence Not for promotional use 97
Insmed Projected EMEA Country Footprint Specific Field Force Structures Reflect Country- Specific Patient Pathways and NTM Management ProtocolsCountry KeyRegional HQ – No Local Commercial OrgInsmed Commercial OrganizationUnder Review - Insmed vs DistributorCustomer facing FTEs grow as country reimbursement comes online*FTEs 2020 2021 2022Field Based Medical 14 18 21Field Based Commercial 10 21 29*ProjectionsNot for promotional use 98
Insmed Projected EMEA Country Footprint Specific Field Force Structures Reflect Country- Specific Patient Pathways and NTM Management ProtocolsCountry KeyRegional HQ – No Local Commercial OrgInsmed Commercial OrganizationUnder Review - Insmed vs DistributorCustomer facing FTEs grow as country reimbursement comes online*FTEs 2020 2021 2022Field Based Medical 14 18 21Field Based Commercial 10 21 29*ProjectionsNot for promotional use 98
Germany First Anticipated Launch & Largest European MarketFour “3-up” territories MSL, RDM & PSP nurse cover identical geography to allow for smooth collaboration between the different parts of the FieldOffice-based PulmonologistsSchleswig- 2 HolsteinMecklenburg- Western PomeraniaBremenHamburg2Lower Saxony 12 1 1Saxony-AnhaltBerlinBrandenburg2German Patient Care ModelExpert CentersNorth Rhein- WestphaliaRheinland- PalatinateSaarland1 Hesse12ThuringiaSaxony2Baden- WürttembergBavaria 1Not for promotional use100
Analytics Enable Focused Commercialization Model in GermanyGeographic analysis based on:• Centers of Excellence• Areas of high NTM prevalence• Existing clinical experience with ARIKAYCESplit into priority focus areas and “white space”Not for promotional use101
Roger Adsett Chief Operating OfficerARIKAYCEJapan Launch UpdateNot for promotional use10210
Commercial Approach: Expansion to Japan
On Track for Anticipated Approval, Mid-Year 2021 Japan Launch2020 March +12 Months ~ 3 months Mid-Year 2021ARIKAYCEJNDA FilingJDNA Approval Price Negotiation Launch2020 June JNDA Approval ~ 3 months Mid-Year 2021Lamira NebulizerNotification Form submitted; considered approvedRequest for health insurance coverageDevice Reimbursement ListingLaunchAnticipated timelines shownNot for promotional use104
“Cost Plus” Approach for Japanese PricingBase Price Premiums Foreign Price AdjustmentARIKAYCEBase price includes manufacturing/transfer price, SG&A, operating profit, distribution cost, consumption taxAdjustments include innovation premium, usefulness premium.Government may adjust to a range of 75- 125% compared to UK, DE & FRBase Price Physician’s Fee Medical treatment fee for LamiraLamira NebulizerBase price includes transfer price, SG&A, operating profit, distribution cost, consumption taxTechnical fee added Government decides final price based on cost plus appropriate physician’s feeNot for promotional use105
Nuances of Japanese MarketPrescriptions are limited to two-week supply for the first year drug is on the marketCo-pay market: approved drugs reimbursed at fixed ratesPhysician offices would exclusively train patients on use of ARIKAYCE with Lamira deviceNot for promotional use106
Building a Strong Presence in Japan 28 People with Japanese AffiliateNot for promotional use107
Engaging Major Medical AssociationsNot for promotional use108
Sales Territories in Japan*Greater OsakaGreater TokyoWest;;;. 7 Reps EAST;;;;. 8 Reps*Jf approvedNot for promotional use 109
Sara Bonstein Chief Financial OfficerFinancial Update & Closing Remarks110
Pipeline ` PRECLINICAL PHASE 1 PHASE 2 PHASE 3 APPROVEDARIKAYCE® (Amikacin Liposome Inhalation Suspension)*Refractory NTM: M. avium complex (MAC)ARIKAYCE® (Amikacin Liposome Inhalation Suspension) Front Line Label ExpansionBrensocatib: DPP1 Inhibitor NCFBE Brensocatib: DPP1 Inhibitor Cystic Fibrosis Brensocatib: DPP1 Inhibitor (IIR) COVID19Treprostinil Palmitil Inhalation Powder (TPIP)Pulmonary Arterial Hypertension (PAH)Internal R&D Various Indications* As a condition of accelerated approval, Insmed plans to conduct an additional clinical study to support full approval.111
Financial Strength to Achieve Our Objectives$641.9M as of 6/30/20Cash and Cash Equivalents>3 Years as of 9/30/20101M* as of 6/30/20Estimated Cash RunwayCommon Shares Outstanding*Excludes stock options, unvested RSUs and shares underlying outstanding convertible notes112
Transformational Growth StrategyWorld Class TeamResearch & Development ExpertiseGlobal Commercial PresenceBusiness Development StrengthBrensocatib NCFBEPipeline TPIP Brensocatib expansionBrensocatib NCFBEARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE Refractory MACARIKAYCE Refractory MACARIKAYCE Refractory MACARIKAYCE Refractory MAC113
Questions & Answers114114
We are committed to bringing forth technologies and medicines in therapeutic areas with the greatest potential to make a difference in patients’ livesThank YouInvestor Relations investor.relations@insmed.com 646-351-0954115
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